tbuckley/cabot-search huggingface dataset:
Abstract 12560: Single Cell RNA Sequencing Signature of Cardiac Allograft Vasculopathy
Authors: Yuko Tada, Sujit Silas Armstrong Suthahar, Vasantika Suryawanshi, Amy Wu, Erpei Wang, Vincenzo Cusi, Klaus F Ley, Paul Kim
Journal: Circulation (2023)

Background: Cardiac allograft vasculopathy (CAV) is one of the major causes of death after heart transplantation (HTx). However, immunological mechanisms of CAV remain incompletely understood. This study aimed to determine distinct immune profiles of CAV compared to HTx patients with normal graft function (CONTROL). Methods: Peripheral blood mononuclear cells (PBMC) obtained from the International Society for Heart and Lung Transplant grade 2 or 3 CAV (n=6), and CONTROL (n=12) patients were analyzed using single cell RNA sequencing (498 genes) on the BD Rhapsody platform combined with 56 protein markers (CITE-seq) and VDJ-seq. Cells were clustered into major cell types using 18 protein markers. Targeted clustering was then performed to determine subclusters using proteomic and transcriptomic data. Results: Proportions of memory B cell (0.5±0.4% vs 1.4±0.8%, p=0.01) and CD16+CD56+ TEMRA CD8 T cell (0.5±0.3% vs 1.0±1.7%, p=0.007) were decreased and proportion of C1q+ nonclassical monocyte (1.0±0.5% vs 0.4±0.3%, p=0.01) was increased in CAV patients compared to CONTROL. In Th1 effector memory CD4 T cell cluster, CAV had a significantly higher proportion of clonally expanded cells (24.1±10.0% vs 11.3±9.2%, p=0.01) characterized by higher expression of NKG7, GZMH, CCL5, and CST7 compared to non-expanded cells in this cluster. Signature genes with the highest positive coefficients determined by LASSO regression to predict CAV (72.2% accuracy) included IFITM3, LAIR2, CD52, IFITM2, NKG7, NAMPT, CD74, F13A1, IL3RA, and RNASE2. IFITM3 and LAIR2 were the best positive predictors for CAV and overexpressed predominantly in CD4 T and CD8 T cells (Figure). Conclusion: CAV demonstrates distinct immune cellular and transcriptomic phenotypes compared to CONTROL. IFITM3 and LAIR2 overexpression in PBMCs may predict severe CAV in HTx patients.
Abstract 16930: Patient Perceptions of Multilevel Nudges About Cardiovascular Medication Refills: A Qualitative Analysis
Authors: Prerna Gupta, Kaitlyn McLeod, Lisa Caputo Sandy, Joy Waughtal, Prateeti Khazanie, Larry A Allen, Pamela Peterson, Sheana Bull, Michael Ho
Journal: Circulation (2023)

Introduction: Nudges are simple messages designed to elicit behavior change. In a multi-center pragmatic clinical trial, we embedded nudge messages into short message service texts (SMS) to encourage patients to refill medications to improve medication adherence. In this study, we assessed patient perceptions of the nudge messages. Methods: We conducted in-depth, open-ended interviews with a sample of English and Spanish speaking patients with cardiovascular disease and documented medication refill gaps enrolled in the clinical trial from a tertiary care academic center, UCHealth, and an urban safety-net hospital, Denver Health. We transcribed interviews and performed content analysis to identify themes. Patients were interviewed about their experiences over the phone using interview guides and perceptions of the nudge messages. Content analysis was done by a trained reviewer to identify themes. Results: Among 12 interviews (4 in Spanish), all appreciated the nudge messages, even though some had successful systems to remind them of medications already. All patients interviewed had no concerns about the messages because they were discreet and respected patient privacy. Some patients felt the health system was caring for them by sending messages. Suggestions for improvement included: 1) medications instructions, such as whether to take them with food; 2) dietary education; and 3) reminders for taking medication in the middle of the day, the doses that were more likely to be missed. Despite liking the messages, most self-reported no change in their medication taking behavior due to reminders they had set up themselves. They did, however, appreciate the nudge messages, and a few patients stated that the messages helped them ‘stay on track’ with refills. Conclusions: Patients appreciated the nudge messages that encouraged them to pick up medication, and generally felt supported by the healthcare system in receiving them. Most patients had no suggestions for improving the nudges. Self-reported behavior change in taking medications was low, though patients’ statements suggested the messages were still helpful with refills. True behavior change will be revealed in the final quantitative analysis of the trial.
Abstract 16942: Organized Thrombus (OTh) Formation Mediated by Disturbed Flow-Induced Endothelial Senescence-Associated Stemness (SAS)
Authors: Sivareddy Kotla, Venkata Subrahman K Samanthapudi, Selina Hernandez Gonzalez, Kaylah Y Perez, Steven Lin, Efstratios Koutroumpakis, Nicolas L Palaskas, Cielito Reyes-Gibby, Sai-Ching Yeung, Robert Dantzer, Craig Morrell, Sunil Krishnan, Shengyu Li, Guangyu Wang, Eduardo N Chini, James F Martin, NHAT TU T LE, Junichi Abe
Journal: Circulation (2023)

Atherosclerotic and high-risk plaques are predominantly localized to vessel wall regions with non-laminar disturbed blood flow (d-flow), leading to the principle that d-flow-, but not laminar flow (l-flow)-driven endothelial cells (EC) dysfunction plays a role in this process. LATS1/2 and YAP are components of the Hippo signaling pathway that are involved in cellular responses to l-flow. The l-flow-mediated inhibition of LATS1/2 activity triggers YAP activation and maintains vascular structure. However, the role of Hippo signaling under d-flow remains unclear. Although both l- and d-flow increased YAP activity, only d-flow decreased LATS1/2 expression. Since the effects of l- and d-flow on EC differ, we studied the role of EC LATS1/2 using EC-specific Lats1 and 2 knock-out (EKO) mice. Within 14 days after inducing Lats1/2 deletion in tamoxifen-inducible Lats1 homo / Lats2 homo EKO mice, all the mice (27/27) died of severe systemic edema, accompanied by increased EC apoptosis and vascular permeability. We generated Lats1 he t / Lats2 homo -EKO mice ( Lats1 het /2 homo -EKO) and induced hypercholesteremia with AAV8-PCSK9 injections and a high-fat diet (HFD). After HFD, we detected plaque erosion-like plaque lesions at the d-flow areas, which revealed strongly fibrin/fibrinogen-positive organized thrombus (OTh) formation without sizeable necrotic cores. In Lats1 het /2 homo -EKO, we found significant increases in 1) EC proliferation, 2) EC apoptosis with senescent phenotype, 3) tissue factor (TF) expression, and 4) inflammation. Therefore, the phenotype observed in Lats1 het /2 homo -EKO represents a unique senescence-associated stemness (SAS) phenotype, which allows EC to escape senescence-induced cell cycle arrest. The EC proliferation induced by depletion of LATS1/2 was YAP-dependent. In contrast, EC senescence induced by CD38-mediated NAD + depletion was YAP-independent. These findings indicate that downregulating LATS1/2 expression-induced SAS leads to OTh via both YAP-dependent and independent mechanisms. OTh plays a key role in human atherosclerosis but is rarely observed in the mouse atherosclerosis model. Lats1 het /2 homo -EKO can provide a valuable platform for studying the mechanism and unique role of EC SAS-induced OTh formation.
Abstract 13829: Assessing the Recovery From COVID-19-Related Disruptions to Cardiovascular-Related Screening Services by Race and Ethnicity
Authors: Christopher Alba, ZhaoNian Zheng, Rishi K Wadhera
Journal: Circulation (2023)

Introduction: The COVID-19 pandemic significantly disrupted routine clinical care in 2020. We aimed to assess recovery from COVID-19’s impacts on health care utilization, affordability, and cardiovascular risk factor screening in 2021, both overall and by race and ethnicity. Methods: We used 2019 and 2021 National Health Interview Survey data-a nationally-representative, cross-sectional household interview survey of US adults ( &gt; 18 years old). Outcomes included measures of health care access, affordability, and cardiovascular risk factor screening. Logistic regression models compared outcomes in 2021 (second year of pandemic) to 2019 (pre-pandemic baseline), adjusting for age and sex. An interaction term for race/ethnicity and year assessed for differential change across racial/ethnic groups. Results: The weighted population size was 250.9 and 253.1 million adults in 2019 and 2021. In 2021, wellness visits significantly decreased for all racial/ethnic groups compared with 2019, a decline most pronounced for Asian adults. Medical financial concerns decreased for White, Black, and Hispanic adults. Blood pressure, cholesterol, and diabetes screening significantly decreased for all groups in 2021 vs. 2019, with the largest declines among Asian adults (see Table 1 and Figure 1 for all results). Conclusions: In this national study of US adults, there were significantly fewer wellness visits and lower rates of cardiovascular risk factor screening in 2021 compared to pre-pandemic levels, overall and across all racial and ethnic groups. These results suggest that policy efforts are needed to improve access and cardiovascular screening as the US emerges from the pandemic.
Abstract 12580: Impact of Zero Coronary Artery Calcium on Downstream Cardiac Testing
Authors: Ethan Y Lin, Rea Alonzo, Jiming Fang, Anna Chu, Levi Elhadad, Shalane Basque, Harindra C Wijeysundera, Kate A Hanneman, Elsie T Nguyen, Michael E Farkouh, Jacob A Udell, Idan Roifman
Journal: Circulation (2023)

Introduction: While coronary artery calcium scoring (CAC) has emerged as a useful tool for cardiovascular disease (CVD) risk prediction, its impact on downstream resource use remains unclear, especially in those with zero CAC. The purpose of this study was to determine the relationship between zero CAC and downstream use of cardiac procedures. Methods: Consecutive CAC scores from two academic hospitals in Toronto, Canada, from 2011 - 2019, were linked to population-based databases. Subjects with zero calcium without previous CVD were subsequently propensity score-matched with a non-CAC-tested control group for age, sex, CVD risk factors and comorbidities relevant to receipt of testing. Downstream cardiac testing, myocardial infarction (MI), stroke, and congestive heart failure (CHF) hospitalizations were compared between the two groups. Results were analyzed using descriptive statistics and Cox proportional hazards regression models. Results: 4,884 patients (Mean 56.8y, SD 11.3) underwent CAC scoring, of whom 2,709 (55.5%) had zero CAC (Mean 52.9y, SD 10.6, 55.4% women). Compared to those not tested at 90 days, zero CAC subjects had similar graded exercise stress test (GXT) (72 tests vs 60, p = 0.29), stress echocardiography (40 vs 32, p = 0.34) and myocardial perfusion imaging (MPS) (26 vs 37, p = 0.15), but higher cardiac MRI (CMR) (48 vs 7, p &lt; 0.001) use. At 3.4 years, GXT (HR 1.24, 95% CI 1.14 - 1.35), stress echocardiography (HR 1.80, 95% CI 1.59 - 2.05) and CMR (HR 3.40, 95% CI 2.55 - 4.53) use was higher in the zero CAC group, whereas MPS (HR 1.08, 95% CI 0.97 - 1.21) and catheterization (HR 1.14, 95% CI 0.91 - 1.44) were similar and PCI (HR 0.59, 95% CI 0.35 - 0.98) and CABG (HR 0.14, 95% CI 0.03 - 0.61) were lower. There was an approximately 5-fold lower rate of MI (HR 0.22, 95% CI 0.10 - 0.51) in the zero CAC group at 3.4 years and no difference in stroke (HR 0.98, 95% CI 0.46 - 2.05) or CHF hospitalizations (HR 1.15, 95% CI 0.53 - 2.48). Conclusion: Zero CAC was associated with higher use of some non-invasive cardiac testing, similar use of catheterization, and reduced PCI, CABG and AMI when compared to a propensity score-matched control group. The results support the utility of a zero CAC in limiting invasive procedures while maintaining an association with reduced cardiac events.
Abstract 19133: Sodium Induced-RGMa Plays a Role in Salt-Sensitive Hypertension
Authors: Selam Desta, Ashley Pitzer Mutchler, Lale A Ertuglu, Mohammad Saleem, Jeanne Ishimwe, Quanhu Sheng, Annet Kirabo
Journal: Circulation (2023)

Salt sensitivity of blood pressure, characterized by blood pressure fluctuations that mirror dietary sodium (Na + ) intake, is an independent risk factor for cardiovascular morbidity and mortality in people with and without hypertension. We previously found that elevated Na + uptake via the amiloride-sensitive epithelial sodium channel (ENaC) in antigen-presenting cells leads to the upregulation of isoleuvoglandins and proinflammatory cytokines ultimately leading to T cell activation and salt-sensitive hypertension. In addition, we also showed that SMAD3 activation plays a role in inflammation and salt-sensitive hypertension. In previous studies, RGMa has been shown to be upstream of SMAD3. Furthermore, previous studies have also shown that knockdown of RGMa leads to reduced levels of TGFβ1-induced SMAD3 phosphorylation. The exact mechanism by which elevated extracellular Na + leads to increased blood pressure remains unknown. We hypothesized that RGMa complexes with TGFβ1R1 to promote SMAD3 phosphorylation ultimately contributing to inflammation in salt-sensitive hypertension. To test our hypothesis, we isolated monocytes from human participants (N =11) and treated them with either high (190 mMol/L) or normal (150 mMol/L) Na + in vitro for 72 hours and subsequently performed bulk RNA sequencing. We found that TGFβ1R1 (8837 ± 780.9 vs. 9688 ± 942.5, p =0.350) and TGFβ1R2 (7012 ± 717.0 vs. 7176 ± 633.9, p = 0.059) were being similarly expressed between high or normal salt treatment. Interestingly, RGMa (2253 ± 441.0 vs. 516 ± 84.1, p &lt;0.001) and TGFβ1 (5118 ± 353.9 vs. 9067 ± 826.4, p = 0.073) were significantly upregulated in human monocytes after high Na + treatment compared to normal salt. To further investigate, we performed an in vivo high Na + treatment by utilizing a rigorous salt-loading/depletion protocol on human participants (N = 9) and conducted single-cell transcriptomic analyses. We found a positive correlation between the changes in pulse pressure and RGMa (r = 0.5154, p = 0.1911). Our data suggest that RGMa mediates Na + -induced inflammation and salt-sensitive hypertension which may reveal a novel therapeutic target.
Abstract 13847: Biomarker-Based Phenomapping in Chronic Stable HFpEF and Exercise Capacity: An Analysis of the RELAX Trial
Authors: Matthew W Segar, Nisha Raiker, Vinayak Subramanian, Ryan Geffin, Kershaw Patel, Ambarish Pandey
Journal: Circulation (2023)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous disease associated with low exercise capacity. Hypothesis: Unsupervised clustering of biomarker data can identify subgroups of individuals with HFpEF and differences in exercise capacity. Methods: The study included participants with chronic, stable HFpEF from the RELAX trial with available serum biomarker data. We used unsupervised hierarchical clustering analysis of 9 serum biomarkers to derive phenogroups of participants with HFpEF. Adjusted linear regression was used to assess the association between cluster membership with peak oxygen consumption (VO2), maximum exercise watts, and VO2 anaerobic threshold. Results: Among 211 participants in the RELAX trial, 3 phenogroups were identified based on the gain in within-inertia. No significant differences were observed in age, sex, or race across phenogroups. Phenogroup 1 (n=136) participants had the lowest burden of CV (cardiovascular) risk factors, including diabetes, anemia, and kidney disease as well as the lowest overall biomarkers levels ( Fig. A ). Phenogroup 2 (n=61) consisted of participants who were older with a higher burden of CV risk factors and fibrosis biomarkers, including galectin-3, collagen-I, and troponin-I levels. Phenogroup 3 (n=14) participants were younger with high burden of CV risk factors and inflammatory biomarkers including aldosterone, CRP, and uric acid. Compared with phenogroup 1, phenogroup 2 and 3 had significantly lower peak VO2, adjusted for traditional CV risk factors [estimate (95% CI): -1.99 (-2.83, -1.16) and -2.31 (-3.66, -0.95), respectively] (Fig. B ). Additionally, phenogroup 3 vs. 1 had lower exercise watts and VO2 anaerobic threshold. Conclusion: Using serum biomarkers, we identified 3 unique phenogroups of patients with chronic, stable HFpEF and significant differences in CV risk factor burden and exercise capacity.
Abstract 12585: The Impact of Remote Patient Monitoring and Digital Therapeutics on Major Clinical Events and Costs in Heart Failure Patients: Early Experience in the Quebec Public Healthcare System
Authors: Emmanuel Marier Tetrault, Paula Aver B Ribeiro, Mouny El Haffaf, Stephanie Bechard, Philippe Brouillard, Emmanuel Bebawi, Shuaiqi Yuan, Thi Xuan Hanh Vo, Michael Khazaka, John Nguyen, Zoe Carrier, Karim El Kamouni, Marie-Pascale Pomey, Francois Tournoux
Journal: Circulation (2023)

Introduction: There is increasing use of digital health solutions in heart failure (HF), but few studies have demonstrated its impact on public healthcare systems in North America. The Continuum project developed a mobile app for remote patient monitoring (RPM) and a digital therapeutics (DTx) solution aimed at assisting clinicians in medication optimization and preventing hospitalizations among HF outpatients. Research Question: Are RPM and DTx cost-effective for care of outpatients with HF? Methods: A 3-month randomized controlled trial for HF outpatients at risk of hospitalisation evaluated the Continuum program versus standard of care alone. This 12-week program included: 1. A self-care app via smartphone or tablet where patients entered vital signs, weight, and HF symptoms; 2. Remote monitoring of these data by clinical nurses; 3. DTx automated medication suggestions sent to the treating medical team; and 4. HF educational modules for patients. Results: A total of 171 patients were included. Preliminary results are available for the first 63 patients that completed the study, 32 intervention (INT) and 31 control (CTRL). Patients were similar in age (70±12 vs 69±13y), NYHA class (II 81 vs 87%), patients with ejection fraction &lt;40% (56 vs 48%) and comorbidities such as diabetes (38 vs 45%; INT vs CTRL). The number of emergency room (ER) visits and/or hospitalisations (all cause) per patient was 0.19±0.47 for the INT group and 0.55±0.89 for the CTRL one (P=0.05). Survival analysis (Figure) showed a trend in favor of the INT group (95 days (CI95% 87-104) vs 78 days (CI95% 68-89); P=0.08). The total cost of healthcare consumption (hospitalizations + ER visits) in the INT group was 134,088 Canadian dollars vs 174,924 in the CTRL group (+30%). Conclusions: Our preliminary results show potential benefits of a mobile app incorporating self-care, remote monitoring, and digital therapeutics in preventing major events in HF outpatients at a reduced cost for the healthcare system.
Abstract 16934: Eicosapentaenoic Acid Inhibits Lipoprotein(a) With Higher Rates of Oxidation Compared to Non-Modified Low-Density Lipoprotein in vitro
Authors: Samuel C Sherratt, Peter Libby, Deepak L Bhatt, Preston Mason
Journal: Circulation (2023)

Background: Lp(a) synthesis is the result of covalent binding of apolipoprotein a to apolipoprotein B on LDL particles. Elevated Lp(a) levels are an independent and causal risk factor for cardiovascular (CV) disease. Atherogenic mechanisms for Lp(a) include increased inflammation due to its associated oxidized lipids. The omega-3 fatty acid (n3-FA) EPA administered as icosapent ethyl reduced CV events in REDUCE-IT. As a potential mechanism, EPA inhibits oxidation of different sized ApoB-containing lipoproteins compared to other n3-FAs. We tested EPA effects on oxidation of lipoprotein samples enriched with Lp(a) compared to control LDL samples. Methods: Lp(a) was enriched to 40% of total ApoB-containing particles from patients with elevated levels by isopycnic centrifugation. Samples of Lp(a) (100 μg/mL) and non-modified LDL were incubated at 37°C for 30 min with EPA (50 μM). Samples were then subjected to copper sulfate-induced oxidation (20 μM) monitored by formation of malondialdehyde (MDA). Results: Lp(a) enriched ApoB particles underwent increased oxidation by 18% after 2 h which was significantly higher than non-modified LDL (13.24 ± 0.47 vs 11.23 ± 0.44 μM, p&lt;0.001). EPA significantly inhibited Lp(a) and non-modified LDL oxidation; after 2 h, EPA inhibited MDA levels by 56% and 76%, respectively (p&lt;0.001). The inhibition of oxidation in both particles with EPA was time dependent. Conclusions: Lp(a) enriched plasma underwent oxidation to a greater extent than non-modified LDL and this process was inhibited in a dose-dependent fashion by EPA. The antioxidant actions of EPA may contribute to reduced events in outcome trials, including in subjects with elevated Lp(a).
Abstract 13849: Characteristics and Outcomes of COVID-19 in Patients With a Left Ventricular Assist Device
Authors: Jorge Fleites, Yoichiro Natori, Jacques Simkins-Cohen, Hoda Butrous, E Joseph J Bauerlein, Anita Phancao, Matthias Loebe, Shweta Anjan, Mrudula Munagala
Journal: Circulation (2023)

Introduction: Patients with left ventricular assist devices (LVAD) are at increased risk for SARS-CoV-2 (COVID-19) complications. There is paucity of literature on factors influencing outcomes of LVAD patients with COVID-19 infection. Methods: A single center retrospective chart review of LVAD patients diagnosed with COVID-19 between March 2020 and March 2023, was performed to define the clinical characteristics and outcomes in this cohort. Demographics, clinical, laboratory, and imaging variables were analyzed. Results: Of 130 LVAD patients, 34 (26.2%) developed COVID-19. The cohort comprised of 27 males (79.4%) with a median age of 63.5 years and BMI of 27.6 (Table 1). Twenty-one had non-ischemic cardiomyopathy (61.8%) with either Heartmate 2 or Heartmate 3 LVADs (38.2% each). Most patients reported NYHA class III (44.1%). The common comorbidities included hypertension (94.1%), hyperlipidemia (79.4%), atrial fibrillation (67.4%), and chronic kidney disease (61.8%). Twenty-eight (82.4%) patients were hospitalized and 2 (7.1%) required mechanical ventilation (Table 2). The average initial and peak INR were 2.39 and 3.26, respectively. No complications of pump hemolysis or thrombosis, or systemic embolisms were noted. Two deaths were reported: one passed away while in the hospital from COVID-19, and another 16 months later due to sequelae of post-COVID pulmonary fibrosis. Conclusions: This is the largest single center study analyzing outcomes of COVID-19 in LVAD patients to date. Our cohort experienced a lower mortality rate from COVID-19 infection compared to prior studies. Larger studies are needed to guide management strategies and analyze long-term outcomes.